Eentrich astd max hardtmankt



Patentecl Aug. 13, 1929.

UNITED STATES PATENT OFFICE.

WINFRID HENTRICH AND MAX IIARDTMANN, OT! XVIESDORF-ON-THE-RHINE, AND RUDOLF KNOCHE, OF LEVERKUSEN-ON-THERHINE, GERMANY, .ASSIGNORS TO GENERAL. ANILENE WORKS, INCL, OF NEW YORK, N. Y., .A CORPORATION OF DELA- WARE.

CONDENSA'IION PBGDUCTS OF THE BENZODIAZINE SERIES AND PROCESS FOR MAKING SAME.

No Drawing. Application filed. January 28, 1928, Serial No. 250,333, and in Germany February 3, 1927.

The present invention concerns new condensation products of the benzo-diazine series and the process of producing the same; They .i'nost probably have thegeneral formula l YNJ in which Y stands for hydrogen or a hydrocarbon residue, R represents any substituent which is attached to the-diazine nucleus with a nitrogen an organically bound sulfur atom, that means a surfur atom which is attached with two valoucies to carbon atoms or an oxygen atom, e. gr-NH substituted. NIL- glI'OLlpS,ll1G OH-group which may be sub stituted by an 'aralkyl or aryl, the SR, or S0 E1 group wherein R stands for an alkyl aralkyl or aryl, and wherein the benzo-diazine may be further substituted in the benzene nucleus.

In accordance with the present invention, appropriate quantities of quinazolines being monohalogenated in a diazine nucleus and wherein the diazine nucleus may be further substituted by a l'iydr-oearbon residue and the benzene nucleus by any substituent, are earn-:od to react with one molecule of such COiDpOUHClS which. possess one or more reactive hydrogenatoins attached to a nitrogen, a sulfur atom which is attached to a C-atom with one valency or an oxygen atom in such a manner that while splitting off hydrogen lniloggenide the above indicated compounds are produced.

The new condensation products thus 0btainable generally are greyish powders which are soluble in water with a yellowish coloration, ifthey contain an acid group; insoluble in water, if they are free from an acid group. The productsfind the most varied application as such or after further decomposition for eX- ample, as intermediate products in the manufacture of dycstuiis or also for the manufacture of pharmaceutical products.

The following examples will illustrate that part of our invention in accordance with which condensation products of similar constitution are-obtained. I

Emmnple 1.16.4t parts by weight ofpowdercd 4-011]oro-quinazoline of the formula SOaH I SQaH after working up in the customary manner,

forms a yellow crystalline powder, which is readily soluble in water after transformation into the sodium salt; its alkaline solutions do not fluoresce. The new compound does not react with nitrous-acid.

Instead of 4-chloro-quinazoline, substitution. products thereof can be employed, such as 6-methyl-4-chloro-quinazoline of inula the for 0r 8-metl1yl-4Echloro-quinazoline of the formula (Compare Finger & Schupp, Journal tiir praktische Ghemie, 74, page 154% and the same, 36, page 155.) The l-amino-S-hydroxynaphthalene-3 6-disult'onic acid in the above example can be replaced by any desired other amino hydroXy naphthalene-sulfonic acid. Condensation products of the benzodiazine series are thus obtained by this modification, which are only slightly or unessentially different in their properties from the compound, described in Example 1.

If amino-aryl-pyrazolones are employed instead of .the a1nin0-hydroxy-napthalenesulfonic acids, compounds are produced, one molecule of which reacts with one molecule of nitrous acid with the -formation of a nitroso compound. Thus, for example, the product of the probable formula (prepared from 6-1nethyl-4-chloro-quinazoline and 1- F-ammo-phenyl) -pyrazolone- (5) -3-carboxyl1c acid according to the directions given in Example 1.) forms a faintly densation is completed. By evaporation and salting out the compound SOBH is obtained, which when dry forms a greyish yellowish powder which is readily soluble in alkalies. The new compound is capable of being diazotized, its diazo compound can easily be salted out.

instead 01 2-chl0ro-quinazoline, its substitution products can be employed, such as for example, (i-methyl-l-phenyl-Q-chloro-quinazoline (see Dissertation 0t Hanschke, Berlin 1899); the l:s -phenylenediamine-3-sultonic acid can be replaced by 1:3-phenylcnedia- 1i'1ine--Lt-sultonic acid or by tlF-ditliliiiiO-diphenyl-3sulfonic acid, or by any desired other amino-sultonic acid or carboxylic acid 01 the benzene or naphthalene series or by amino-hydroxy naphthalene sulfonic acids or amino-aryl-pyrazolones; when using the last two components, isomers of the compounds described in Example 1 are obtained, which possess analogous properties, but in general are more readily soluble.

When instead of 2-chloro-quinazoline the 4-chloro-quinazoline employed in Example 1 or its substitution products substituted in the benzene nucleus are condensed with 1: 1- phenylenediamine-El-sulfonic acid or similar compounds, the reaction already takes place at 40 C. with the formation of an isomer of the products described in the first section of Example 2.

Emma- 9Z6 3.23.9 parts by weight of 2- amino-5-hydroxy naphthalene-T-sultonic acid and 13.6 parts by weight of crystallized sodium acetate are covered with 700 parts of hot water. The amino-naphthol sultonic acid is dissolved by the addition of caustic soda solution; the solution should only show quite weakly alkaline reaction. 20.9 parts by weight of (5-nitroA-chloro-quinazoline are introduced into the well stirred solution at 40 C. lhe condensation proceeds very quickly accompanied by a yellow coloration of the solution; the condensation product of the probable tormula is precipitated in yellow leaflets towards the end of the reaction; on working up, it represents a yellow powder, which is readily soluble in hot water and can be salted out there- OaN- 1,724,ose

from, it does not react with nitrous acid, and yields on reduction with'iron and acetic acid the corresponding amino compound as a grey substance, which can be diazotized and likewise be coupled with diazo compounds.

Instead of Q-amino-5-hydroXy-naphthalene-7-sulfonic acid, other amino-naphtholsulifonic acids or also amino-aryl-pyrazolones or amino-sulfonic acids or rarboxylic acids of the benzene or naphthalene series can be einployed. Thus, for example, the compound (prepared by condensing one molecule of 4- amino--1-hydro: y benzcne-2-carboxylic acid with one molecule of 6-nitrol-chloro-quinazoline according to the direction of Example 3) is a grey-yellowish powder, diliicultly solu ble in water, but easily soluble on heating in the presence of alkalies and can easily be saltedout from the solution. On reduction for example, with sodium hydrosullide the corresponding amine compound is produced as a grey diazotizable powder. Furthermore also more complex amino compounds, such as dehydaO-thio-toluidine-suli onic acids, react smoothly with halogen quinazolines such as 6-nitro-chloro-quinazoline.

In order to prepare the compound dichloro-l:4-phenylene-diamine (in which case the diazotizable compounds:-

O NH- Ne o we (In a a is formed as a yellowish powder), 2-amino-5-' hydroXy-naphthalene, 1-amino-7-hydroxynaphthalene or aliphatic amines.

In order to prepare the compound 4lchloro-6-nitro-quinazoline is dissolved in benzene, and dry ammonia is passed through the solution with stirring at C. until the presence of chloro-nitro-quinazoline can no longer be detected. The product forms a crystalline yellowish powder, Which .is soluble with difliculty in most organic solvents.

Example 4.-10.8 parts by weightof 1 i l. phenyleue-diainine aredissolved in 1.50 vol.- umes of benzene, 16A parts by weight of anhydrous sodium acetate are added and 451.8

parts by weight of (i-nitro-l-chloro-quinazoline are introduced at 50 C. with stirring,

whereupon the solution gradually assumes a yellow coloration.- The compound thus produced 1 N02 OzN is precipitated as a yellow amorphous powder, which 1s insoluble 1n the customary solvents;

by reduction, i. e., with stannous chloride in glac1al acetic ac1d suspension, the corresponding tetrazotizable base 1s obtained.

In this example the l :l-phenylenediamine can also bereplaced by 2:el-diamino-toluene or by naphthylene-diamine. In order to link up ethylene diamine, the process is advantageously carried out in aqueous solution with the employment of the dia-Inine itself asithe acid-absorbing agent.

Emamplc 5.31.9 parts my weight of lamino-8-hydroXy-naphthalene-3 6 disulitonic acid are dissolved with 13.6 parts byweight of crystallized sodnunacetate in 700 parts of water. 21.4 parts by weight of the linear 4-chloro-n aphthodiazine are introduced at G. and thesolution is stirred, finally with raising of the temperature to 7 0 C. until the condensation is completed. The new compound dissolves in hot water with a beautiful yellow coloration; it can be salted out therefrom, but is precipitated at first as a jelly; it couples with one molecule of a diazo compound (for example with diazo benzene) to a reddish violet. The said naphthodiazine can also be condensed under similar conditions with any desired other sulfonated or carboxylated amines or diamines. Unsulfonated amines, such as aniline, 3-nitraniline and the like are condensed advantageously, for example in toluene at to 80 C. with stirring, but otherwise analogously to the process of the second section of Example 3.

Ewa/lnple 6.87.6 parts by weight oi 1 (4t amino-benzoyl) -amino-8-hydroxy naphthalene-3:6-disulfonic acid and 27.2 parts by weight of crystallized sodium acetate are dis solved in water to a concentrated solution an d 32.6 parts by weight of 4 4l-diehloro-6 (S-(liquinazolyl (most finely sieved), are added thereto at 50 O.

The formation of the compound l H? lily-0:0 O C-NH on O l.... Y1...

4-aminobenzoyl-l-amino-8-hydroxynaphthalene-3 6-disulfonic acid, two molecules of any desired other similar or dissimilar amines can be condensed under similar conditions.

Example 71-41 parts by weight of 4-ehlor0- quinazoline and 56 parts by weight of 1- amino-anthraquinone are dissolved in nitrobenzene and heated with or without the addition 01" an acid-absorbing agent, such as .t'or example, potassium acetate, for several hours to 130 C. On cooling the product is filtered and washed with ether. The new compound is a reddish-brown powder, which dissolves in sulfuric acid with a yellow coloration. recrystallization from glacial acetic acid it melts at 230 to 232 C. (uncorrected).

Other amino anthraquinones can also be condensed with e-chloro-quinazoline or 2- chloro-quinazoline or derivatives thereof un der similar conditions. Thus, for example, the product obtained from two molecules of t-chloro-quinazoline and one molecule of 1 5-diamino-anthraquinone is a violet black powder, which dissolves in sulfuric acid with a brilliant green coloration and melts above 285 C.

1-amino-5-benzoyl-amino-anthraquinone or similar compounds, as well as amino anthraquinone sulfonie acids can likewise be successfully employed.

Ewamp e 8.22. lparts by weight of the acid sodium salt of 5-sulfino-2-hydroxy-benzoic acid are dissolved in a small quantity of water; 13.6 parts by weight of crystallized sodium acetate are added thereto, then 20.9 parts by weight of finely divided 6-nitrotehloro-quinazoline are introduced at 50 0., and the whole is heated with continued stirring, finally to 60 C. until the starting materials have disappeared. After cooling, mineral acid is added until acid reaction appears and a little salt. The new compound of the probable formula:

o so2 on OaN- k ([JH .0011

forms a yellowish powder, soluble in hot water; it can be reduced with iron and acetic acid to the corresponding amine compound. After reduction, the reaction mixture is advantageously rendered alkaline with caustic soda while heating, filtered, and the amino compound is isolated from the filtrate by acidifying and concentrating; it forms a grey diazotizable powder. I

Two molecules of 6-nitro-4-chloro-quinazoline react in aqueous solution at 30 to 40 C. in the presence of sodium acetate with one molecule er dithioglycol, which is advantageously dissolved in a little alcohol before being added.

The compound thus obtained of the probable formula is a yellow powder, insoluble in water.

One molecule of 4-n1tro-l hydroxynaphthm lene-5-sulfonic acid can be condensed. with one molecule of 6-nitro-4-cliloroquinazoline in a quite analogous manner to that described in Example 8; the new compound thus ob tained of the probable formula in which Y stands for hydrogen or the residue of a hydrocarbon; R represents any substituent which is attached to the diazine nucleus with a nitrogen or an organically bound sulfur atom or with the oxygen atom of an arylcry or aralkyloxy residue and wherein the benzodiazine may be further substituted in the benzene nucleus, which process comprises reacting upon a monohalogenated quinazoline and wherein the diazine nucleus may be further substituted by a hydrocarbon residue and the benzene nucleus by any substituent with one molecule of the compound of the general formula HR in which formula H represents a reactive hydrogen and R repre sents any substituent which is attached to the reactive hydrogen atom with a nitrogen or an organically bound sulfur atom or with the oxygen atom of an aryloxy or aralkyloxy residue 2. The process of producing a condensation product of the probable formula SO3H' sonar which process comprises reacting upon t chloro-quinazoline with l-amino-8-hydroxy naphthalene-lddisulfonic acid.

3. As new products the compounds of the general formula /C\:LY l lit/r wherein Y stands for hydrogen or the residue of ahydrocarbon; R represents any substituent which is attached to the diazine nucleus with a nitrogen or an organically bound sulfur atom or with the oxygen atom of an aryloXy or aralkyloxy residue wherein the benzodiazine may be further substituted in the benzene, being generally greyish powders soluble in water with a yellowish coloration if they contain an acid group, insoluble in water if they are free from an acid group.

l. As a new product the compound of the probable formula e ii' being a yellow crystalline powder, readily soluble in water after transformation into thesodium salt, in alkaline solution exhibitmg no fluorescene and not reacting with 'ni-' trous acid.

In testimony whereof we have hereunto set our hands. a

,WINFRID HENTRICI-I.

MAX HARDTMANN RUDOLF KNOOHE 

